PMID- 22665768
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20211203
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 25
DP  - 2012 Jun 19
TI  - Temporal expression of microRNA cluster miR-17-92 regulates effector and memory 
      CD8+ T-cell differentiation.
PG  - 9965-70
LID - 10.1073/pnas.1207327109 [doi]
AB  - MicroRNAs are important regulators of various developmental and physiological 
      processes. However, their roles in the CD8(+) T-cell response are not well 
      understood. Using an acute viral infection model, we show that microRNAs of the 
      miR-17-92 cluster are strongly induced after T-cell activation, down-regulated 
      after clonal expansion, and further silenced during memory development. miR-17-92 
      promotes cell-cycle progression of effector CD8(+) T cells, and its expression is 
      critical to the rapid expansion of these cells. However, excessive miR-17-92 
      expression enhances mammalian target of rapamycin (mTOR) signaling and strongly 
      skews the differentiation toward short-lived terminal effector cells. Failure to 
      down-regulate miR-17-92 leads to a gradual loss of memory cells and defective 
      central memory cell development. Therefore, our results reveal a temporal 
      expression pattern of miR-17-92 by antigen-specific CD8(+) T cells during viral 
      infection, the precise control of which is critical to the effector expansion and 
      memory differentiation of CD8(+) T cells.
FAU - Wu, Tuoqi
AU  - Wu T
AD  - Emory Vaccine Center, and Department of Microbiology and Immunology, Emory 
      University School of Medicine, Atlanta, GA 30322, USA.
FAU - Wieland, Andreas
AU  - Wieland A
FAU - Araki, Koichi
AU  - Araki K
FAU - Davis, Carl W
AU  - Davis CW
FAU - Ye, Lilin
AU  - Ye L
FAU - Hale, J Scott
AU  - Hale JS
FAU - Ahmed, Rafi
AU  - Ahmed R
LA  - eng
SI  - GEO/GSE34218
GR  - T32AI074492/AI/NIAID NIH HHS/United States
GR  - AI080192/AI/NIAID NIH HHS/United States
GR  - P01 AI080192/AI/NIAID NIH HHS/United States
GR  - R37 AI030048/AI/NIAID NIH HHS/United States
GR  - T32 AI074492/AI/NIAID NIH HHS/United States
GR  - AI030048/AI/NIAID NIH HHS/United States
GR  - R01 AI030048/AI/NIAID NIH HHS/United States
GR  - N01 AI030048/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120604
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (MIR17HG, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*cytology/immunology
MH  - Down-Regulation
MH  - Gene Silencing
MH  - Humans
MH  - *Immunologic Memory
MH  - Lymphocyte Activation
MH  - MicroRNAs/*genetics
MH  - RNA, Long Noncoding
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3382487
COIS- The authors declare no conflict of interest.
EDAT- 2012/06/06 06:00
MHDA- 2012/09/11 06:00
PMCR- 2012/12/19
CRDT- 2012/06/06 06:00
PHST- 2012/06/06 06:00 [entrez]
PHST- 2012/06/06 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
PHST- 2012/12/19 00:00 [pmc-release]
AID - 1207327109 [pii]
AID - 201207327 [pii]
AID - 10.1073/pnas.1207327109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):9965-70. doi: 
      10.1073/pnas.1207327109. Epub 2012 Jun 4.